Although variations in size of secretion granules have been noticed for approximately a centruy, granules have generally been assumed to be constant in size and of unitary structure. We have been using the pancreas as an experimental system in order to reevaluate this concept of the secretion granule and have considered the possibility that granules are dynamic structures whose size and content can vary. Recent experiments in our laboratory indicate that the size distribution of the zymogen granule varies with physiological and developmental state. For example, granules in the newborn rat are extremely large, about 6 times the volume of adult sized granules, and undergo dramatic decreases in size during the first weeks of postnatal life. A similar but less dramatic decrease in granule size (about a 55% decrease in volume) is seen in adult rats in response to feeding after a prolonged fast. We intend to analyze by quantitative electron microscopy the size distributions of granules during the perinatal period and during active secretion in order to characterize how granule populations change size with changing developmental and physiological state. We have considered two mechanisms for changing granule populations: 1) replacement of one granule size class by another of different size, and 2) an actual change in the size of individual granules. Because these changes are characterized by shifts in normal distributions of granule sizes, it appears that the size of both new and old granules changes with changing state. We plan to further test these possibilities by examining changes in the size, number, and radioactivity of granules whose proteins have been labeled with tritiated leucine and visualized by electron microscopic autoradiography. Changes in the size of zymogen granules have not been appreciated in the past and may have an important impact on our understanding of the way in which the pancreas secretes digestive enzymes.